Manivannan, S (2012) Design, Development of a Novel Transdermal Drug Delivery System as Wound Dressing. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
Transdermal delivery is one of the common and frequently used drug delivery routes. Transdermal route has gained more attention in drug delivery due to its flexibility and convenience in comparison to other routes of delivery and it is one of the suitable, convenient, safe and economic way to deliver drug. Herbal drugs are safe and also called as botanical medicine or phytomedicine obtained from any plant portion. Herbal medicines can also be formulated as tablets, capsules, liquids, infusions, ointments, extracts like allopathic systems. Herbal medicines are commonly used because of the minimized or no side effects and cost effectiveness. Wound healing is a complex and dynamic process with the wound environment changing with the changing health status of the individual. Transdermal drug delivery is commonly used system in the management of wound, pain and various inflammations. The overall aim and objective of the development of transdermal drug delivery system for herbal drugs with wound healing property were i) To make an alternate to synthetic/allopathic drugs which may produce severe side effects and toxicity. ii) Herbal drugs were not successfully employed because of the low bioavailability. So to increase the bioavailability of herbal drugs transdermal drug delivery systems were chosen leading to patient compliance. iii) Filing of patents may be possible. To achieve there objectives novel transdermal drug delivery systems for herbal drugs with wound healing property were developed. Calotropis gigantea and Ficus racemosa were selected for this present study. For calotropis gigantea, aerial parts and for Ficus racemosa, bark were used for the research. The pharmacognostical studies were performed for the above two plants. Macroscopic and microscopic tests were performed. Ash value, extractive value and loss on drying tests were performed and reported. Phytochemical factors were studied and reported. The quantitative determination of phytoconstituents was carried out by using methanolic extract of plants. Ficus racemosa contains alkaloids 3.31%w/w, bitters 7.16%w/w, flavonoids 0.64%w/w and tannins 43.49% w/w. Calotropis gigantea L contains alkaloids 35%w/w, bitters 33.71%w/w, flavonoids 0.27%w/w and tannins 1.37%w/w. The extracts were subjected to fractionation. The bioactive fractions were collected. The active fractions were analyzed by TLC. Pharmacological studies were carried out for six fractions, 3 from calotropis gigantea and 3 from Ficus racemosa. From the fractions FRfr3 and CGfr3 possessed predominant wound healing activity. So these fractions were considered for further studies. The wound healing mechanism for these two plants was based on anti-inflammatory activity. The anti-inflammatory activity was determined by carrageenan induced rat model. The wound healing studies were performed by excision and incision model. The animals were grouped in 8 groups. Positive control, control, CGFR1, CGFR2, CGFR3, FRFR1, FRFR2 and FRFR3. Percentage of wound healing in excision wound model (% wound closure), breaking strength of wound in incision wound model were determined and reported. The compounds were isolated from the CGFR3 and FRFR3 fractions and structures were elucidated by interpreting IR, Mass and NMR datas. Transdermal patches were prepared by solvent evaporation method for TPCGFR3, TPFRFR3 and its combination TPCGFRFR3. A biocompatible nature polymer protonal LF10/60 was used to prepare the matrices. The formulated transdermal patches were evaluated for drug content, thickness, folding endurance, percentage moisture content, percentage moisture uptake, water vapor permeability, in-vitro release and in vivo tests. In vitro cytotoxicity studies were carried out. From the results it was observed that the physical parameters were found to be satisfactory. The in vitro release studies indicated that the drug was released in controlled fashion. Transdermal formulations were exposed to in vitro cytotoxicity studies in Balb/c 3T3 cell line using direct contact method. Quantitative evaluation using MTT assay for the test item CGFR3 (TPCGfr3), FRFR3 (TPFRfr3) and CGFR3 + FRFR3 (TPCGFRfr3) and Blank (Placebo) showed a viability of 86.84%, 85.53%, 86.84% and 92.76% respectively. The obtained values indicated that the transdermal patches were non-cytotoxic. In vivo studies, the transdermal patches CGFR3, FRFR3 and FRFR3+CGFR3, significantly improved the wound healing activity in both excision and incision models when compared with control group. All the drug transdermal systems showed significant reduction in wound area and significant increase in wound breaking strength. In vivo studies suggested that the combination of the herbals drugs possessed better pharmacological action than the individual drugs formulations. Stability studies conducted for 90 days at 40ºC ± 2ºC / 75% ± 5% RH confirmed that all the transdermal patches were stable and good release in drug content. The drug content reduced from 92.1 ± 0.1 % to 91.4 ± 0.4, 93.3± 0.3 % to 92.3 ± 0.3% from the period of 3 months for TPFRfr3, TPCGfr3 and TPCGFRfr3 respectively. The in vitro release reduced from 82.6±1.6 % to 81.7±1.2 %, 86.6 ±1.6% to 85.4±0.8 %, 90.8 ±1.2 to 89.6 ±1.4 from the period of 3 months for TPFRfr3, TPCGfr3 and TPCGFRfr3 respectively. The present studies indicated - Enhancement in wound healing activity - Absence of cytotoxicity. Although required qualities were achieved with herbal formulations TPCGFR3 and TPFRFR3, TPCGFRFR3 exhibited better activity in both in vitro and in vivo studies. The in vitro toxicity studies revealed that the formulations were non-cytotoxic. Hence it can be concluded that the newly developed formulation-transdermal drug delivery system of herbal drugs (CGFR3, FRFR3 and CGFR3+FRFR3) was considered to be ideal and effective in the management of wound healing. CONCLUSION: The present work is based on the transdermal drug delivery of herbal drugs. • Two plants Ficus racemosa and Calotropis gigantea were selected for wound healing activity. • From each plant, 3 fractions, totally 6 fractions were isolated successfully. From the pharmacological studies, it was proved that both plants possess wound healing activity but fractions FRfr3 and CGfr3 of Ficus racemosa and Calotropis gigantea respectively were found to possess prominent and predominant wound healing activities. • Hence transdermal drug delivery systems for fractions of Ficus racemosa (FRfr3), Calotropis gigantea (CGfr3) and its combination (FRfr3 +CGfr3) were formulated and evaluated. The formulations successfully released active part in a controlled fashion up to 24h. • The bioavailability of the herbal drugs was enhanced by transdermal drug delivery approach. The three formulations exhibited the ideal characters for transdermal drug delivery systems including in vitro and in vivo studies. • In vitro cytotoxicity studies confirmed the absence of cytotoxicity for the transdermal patches. • The transdermal patches CGFR-3, FRFR-3 and FRFR-3+CGFR-3 showed notable wound healing activity in both excision and incision wound models when applied topically. Among three test patches FRFR-3+CGFR-3 exhibited effective wound healing activity, followed by FRFR-3 and CGFR-3 in both Excision and Incision wound models. This maximal effect of FRFR-3+CGFR-3 might due to the synergistic action of CGFR-3 and FRFR-3. • Stability studies conducted for 90 days at 40ºC ± 2ºC / 75% ± 5% RH confirmed that all the transdermal patches were stable. • Hence, it can be concluded that the newly developed formulation-transdermal drug delivery systems with herbal drugs (Ficus racemosa and Calotropis gigantea) is considered to be potential and effective in the management of wound healing and its related disease conditions.
| Item Type: | Thesis (Doctoral) |
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| Uncontrolled Keywords: | Wound Dressing, Design, Development, Novel Transdermal Drug Delivery System. |
| Subjects: | PHARMACY > Pharmacy Practice |
| Depositing User: | Devi S |
| Date Deposited: | 27 Jun 2017 10:14 |
| Last Modified: | 13 Sep 2022 16:02 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/439 |
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